PROJECT SUMMARY Urinary incontinence is prevalent, morbid, and costly ($20 billion/year in 2000), especially for older adults who suffer from the most common type: urgency incontinence (UUI). Generally ascribed to 'bladder spasms' (detrusor overactivity), UUI's actual causes are unknown, and therapy remains inadequate with little improvement in the last 50 years. One of the most common reported forms of UI symptoms is situational incontinence, described as urgency and/or leakage when confronted with specific common situations, e.g. approaching the front door or doing dishes. Although well documented, it is difficult to assess and quantify, and is poorly studied. We believe that people who experience situational incontinence have a conditioned, Pavlovian response to environmental triggers or `cues'. Surveys have shown that `cue' scenarios are a major cause of urgency and leakage in UUI sufferers, but are not addressed by current therapies. Our recent studies have focused on brain control of the bladder, in particular how this control system fails in those with urgency incontinence. We would expect different brain mechanisms to fail and compensate in the setting of different types of urgency (i.e. urgency with different causes). We have succeeded in reproducing urgency and detrusor overactivity in response to photographs of personalized cue and safe scenarios. Thus, we should now be able to elicit situational urgency in an MRI scanner, and thereby ascertain the brain mechanisms involved. Understanding the brain's role in UUI is critical. We propose an exploratory study to investigate, for the first time, the role of the brain in cue-provoked urgency incontinence. Our transdisiplinary collaboration combining personalized cue development and functional MR imaging makes this possible. Our main aim is to recreate situational urgency in the MRI scanner while simultaneously recording brain activity during exposure to each participant's personalized urgency/leakage-provoking scenarios and 'safe' situations. This will allow us to further develop a basic model of how the brain reacts to situations that trigger urgency incontinence. Such understanding will complement our current working model of how the brain processes urgency resulting from bladder fullness without external stimuli. To accomplish our aims, we will recruit 25 women with situational urgency incontinence to identify situational triggers. All will undergo simultaneous urodynamics and fMRI scanning during exposure to their personal pictorial cue and safe scenarios. New knowledge about this significant contributor to UUI will allow development of therapeutic approaches to complement and enhance the efficacy of current UUI therapy and reduce symptom burden for many sufferers.